Stem cells, which possess the unique ability to undergo self-renewal and differentiation into tissue-specific cells, give rise to all tissues in the body. Unlike embryonic stem cells which can differentiate into many different cell types, tissue specific stem cells can only form cells unique to one tissue. Recent advances in stem cell molecular biology techniques have enabled researchers to examine the concept that a malignant tumor can be formed and maintained due to the presence of a small number of cancer-specific stem cells.
Stem cells can renew themselves. This self-renewal process of all stem cells, including tumor stem cells, is known to be very tightly regulated. Many reports in the past several years have confirmed that small populations of cancer stem cells have been found in a variety of cancers including glioma, breast, pancreas, ovarian, hepatocellular carcinoma, and melanoma, to name a few. Furthermore, it has also been widely reported that current cancer chemotherapeutic agents which can successfully kill differentiated tumor cells are actually ineffective against the small population of cancer stem cells which may be a contributing factor to the regeneration of cancer cells after chemotherapy. These agents act by inhibiting a wide variety of known cell signaling, growth regulation, and cell death mechanisms within these normally differentiated cancer cells. Several studies have suggested that long-term ineffectiveness of chemotherapy agents against cancer stem cells may be due to their lack of penetration into these cells. Although early in development, this hypothesis may at least partially explain the regeneration of tumor cells after chemotherapy.
Because of its nature, radiation may afford a higher degree of efficacy in killing cancer stem cells. Although certain tumors can be effectively treated with external beam radiation, in many cases, the tumors reappear at a later time. In addition to chemo-resistance of cancer stem cells, it is now known that glioma stem cells are also 30% more radio-resistant than regular glioma cells. This finding is based on radiation applied via external beam. Systemically administered radiotherapeutics that can target normally differentiated cancer cells may still hold a significant advantage over chemotherapeutics due to their collateral killing ability, wherein radiation emanating from surrounding tumor cells has the ability to kill a lone stem cell via a “cross-fire” effect (The “cross-fire” effect is a theory that the radioactive compounds can kill both the cancer cells to which they attach and the adjacent tumor cells).
In addition, systemically administered radiotherapy gives a prolonged and continuous radiation exposure which appears to be more effective in tumor cell killing than is intermittent external radiation therapy. It is even more probable that if a systemically administered radiotherapeutic agent could actually target the cancer stem cells and penetrate their membrane, the radiotherapeutic agent would have a better chance of killing the cancer stem cell and preventing its eventual regrowth.
Accordingly, there is a need for radiotherapeutic agents that can treat cancer either by themselves or in combination with external beam radiotherapy. In addition, there is a need for new methods of identifying stem cells, both in vitro and in vivo.